PMID- 33729475
OWN - NLM
STAT- MEDLINE
DCOM- 20211001
LR  - 20211001
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 62
IP  - 3
DP  - 2021 Mar 1
TI  - Modulating Ocular Surface Pain Through Neurokinin-1 Receptor Blockade.
PG  - 26
LID - 10.1167/iovs.62.3.26 [doi]
LID - 26
AB  - PURPOSE: The purpose of this study was to test the role of substance P (SP) and 
      its receptor neurokinin 1 (NK1R) on ocular surface pain. METHODS: Eight-week-old 
      C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 
      M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 
      10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye 
      wiping test was used to quantify ocular surface pain. SP content was quantified 
      in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the 
      cornea. Corneas were immunostained for beta3-tubulin and NK1R, or CD45, to quantify 
      leukocyte infiltration. RESULTS: TAC1-KO mice displayed a significant reduction 
      of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL 
      fosaprepitant applied topically to WT mice reduced ocular pain as compared to 
      vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia 
      only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or 
      oxybuprocaine reduced corneal nociception when compared to vehicle or 
      fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP 
      content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 
      0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of 
      NK1R and beta3-tubulin was detected in mouse corneas. CONCLUSIONS: Topical 
      administration of the NK1R antagonist fosaprepitant effectively reduces ocular 
      surface nociception by decreasing SP release in the tear fluid and TG, and 
      corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the 
      treatment of ocular pain.
FAU - Lasagni Vitar, Romina Mayra
AU  - Lasagni Vitar RM
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
FAU - Barbariga, Marco
AU  - Barbariga M
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
FAU - Fonteyne, Philippe
AU  - Fonteyne P
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
FAU - Bignami, Fabio
AU  - Bignami F
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
FAU - Rama, Paolo
AU  - Rama P
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
FAU - Ferrari, Giulio
AU  - Ferrari G
AD  - Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele 
      Scientific Institute, Milan, Italy.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Morpholines)
RN  - 0 (Neurokinin-1 Receptor Antagonists)
RN  - 0 (Ophthalmic Solutions)
RN  - 33507-63-0 (Substance P)
RN  - 6L8OF9XRDC (fosaprepitant)
SB  - IM
MH  - Administration, Ophthalmic
MH  - Animals
MH  - Cornea/innervation
MH  - Corneal Diseases/*prevention & control
MH  - Disease Models, Animal
MH  - Eye Pain/*prevention & control
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Morpholines/*therapeutic use
MH  - Neurokinin-1 Receptor Antagonists/metabolism/*therapeutic use
MH  - Nociception/drug effects
MH  - Ophthalmic Solutions
MH  - Substance P/metabolism
MH  - Tears/metabolism
MH  - Trigeminal Nerve/metabolism
PMC - PMC7980039
COIS- Disclosure: R.M.L. Vitar, None; M. Barbariga, None; P. Fonteyne, None; F. 
      Bignami, None; P. Rama, (P); G. Ferrari, (P)
EDAT- 2021/03/18 06:00
MHDA- 2021/10/02 06:00
PMCR- 2021/03/17
CRDT- 2021/03/17 12:34
PHST- 2021/03/17 12:34 [entrez]
PHST- 2021/03/18 06:00 [pubmed]
PHST- 2021/10/02 06:00 [medline]
PHST- 2021/03/17 00:00 [pmc-release]
AID - 2772405 [pii]
AID - IOVS-20-31960 [pii]
AID - 10.1167/iovs.62.3.26 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2021 Mar 1;62(3):26. doi: 10.1167/iovs.62.3.26.